title: IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells.
abstract: Genome-wide association (GWA) studies revealed a number of single nucleotide polymorphisms (SNPs) significantly associated with type 1 diabetes (T1D). In an attempt to confirm some of these candidate associations, we genotyped 2046 Caucasian patients and 2417 normal controls from the United States for SNPs in five genomic regions. While no evidence was obtained for four genomic regions (rs2929366/NM_144715 on chromosome 3, rs9127/Q7Z4C4 on chromosome 5, rs1445898/CAPSL on chromosome 5 and rs2302188/NM_033543 on chromosome 19), we provide strong evidence for association between T1D and multiple SNPs in the IFIH1 linkage disequilibrium (LD) block on chromosome 2q. Among the 10 SNPs genotyped for the 2q region, four SNPs located within the IFIH1 gene or at the 5' region of IFIH1 showed significant association with T1D in the Georgia population [odds ratio (OR) = 1.7-1.9] with the best P-value found at SNP rs1990760 (P = 8 x 10(-8) and OR = 1.9). Several SNPs outside of the IFIH1 gene also showed significant but weaker associations. Furthermore, IFIH1 gene expression levels in peripheral blood mononuclear cells are significantly correlated with IFIH1 genotypes, and higher IFIH1 levels are found in individuals with the susceptible genotypes (P = 0.005). Thus, both genetic association and gene expression data suggest that IFIH1 is the most plausible candidate gene implicated in T1D in this LD block.
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Siyang
authors.initials: S
authors.lastname: Liu
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wang
authors.forename: Yulan
authors.initials: Y
authors.lastname: Jin
authors.forename: Robert
authors.initials: R
authors.lastname: Podolsky
authors.forename: M V Prasad Linga
authors.initials: MV
authors.lastname: Reddy
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pedersen
authors.forename: Bruce
authors.initials: B
authors.lastname: Bode
authors.forename: John
authors.initials: J
authors.lastname: Reed
authors.forename: Dennis
authors.initials: D
authors.lastname: Steed
authors.forename: Steve
authors.initials: S
authors.lastname: Anderson
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Andy
authors.initials: A
authors.lastname: Muir
authors.forename: Leigh
authors.initials: L
authors.lastname: Steed
authors.forename: Diane
authors.initials: D
authors.lastname: Hopkins
authors.forename: Yihua
authors.initials: Y
authors.lastname: Huang
authors.forename: Sharad
authors.initials: S
authors.lastname: Purohit
authors.forename: Cong-Yi
authors.initials: CY
authors.lastname: Wang
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Steck
authors.forename: Annalisa
authors.initials: A
authors.lastname: Montemari
authors.forename: George
authors.initials: G
authors.lastname: Eisenbarth
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
mesh_terms: D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1